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Potential Next Steps

Jay E. Slater, MD

Director, DBPAP

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Today’s presentations• Background

• Allergenics efficacy reviews– Panel 1, 21 CFR 601.25 (1974-1979)– Panel 2, 21 CFR 601.26 (1982-1983)

• Current evaluation process (2003-2011)

• Safety of allergenic extracts

• Assessments

• Next steps

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Internal review determinations• Table 1. Use in Diagnosis and Treatment Addressed

in Literature (n = 480)

• Table 2. Foods: Use in Diagnosis Addressed in Literature (n = 134)

• Table 3. Non-food: Use in Diagnosis Addressed in Literature (n = 73)

• Table 4. Minimal or No Literature Relating to Use in Diagnosis and Treatment (n = 566)

• Table 5. Potential Safety Issues (n = 16)

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Documents available

• Review panel reports– http://www.fda.gov/BiologicsBloodVaccines/Allergenics/ucm272115.htm

• Tables– http://www.fda.gov/downloads/AdvisoryCommittees/

CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/AllergenicProductsAdvisoryCommittee/UCM274718.pdf

• FR notice (instructions for comments)– http://www.gpo.gov/fdsys/pkg/FR-2011-09-26/pdf/2011-24598.pdf

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Discussion points

• Comments on– the review process so far; – the decision to list non-standardized

allergenic products in five tables according to the evidence collected; and

– the possible disposition of the categories of products identified in the Tables

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Paths forward

• 21 CFR 601.25 and 601.26

• Other approaches

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Paths forward

• 21 CFR 601.25 and 601.26• Established approach• Basis for previous efficacy/safety reviews• But - it is difficult to assess non-standardized

products using data that relate to “general” product type. (For a new approval today, we would require individualized showing for a manufacturer’s product.)

• These regulations apply to products licensed before 1 July 1972 – and not to those licensed after that date.

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Assessing non-standardized products “generally”

• The “general” data are comprised of:– Conclusions from case reports, not studies– Interpretation and application of cross-

reactivity data– Conclusions applied “generally” to multiple

manufacturers

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Non-standardized allergenic products licensed after 1 July 1972

• Three of seven manufacturers obtained their licensed for non-standardized allergenic extracts late 1972 to 1974.

http://www.fda.gov/downloads/BiologicsBloodVaccines/UCM149969.pdf

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Paths forward

• 21 CFR 601.25 and 601.26

• Other approaches: – Use other regulations to address evidence of

efficacy issues (Tables 4 and 5) along with safety issues (Table 5)

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Paths forward

• Reasons to take action on the basis of efficacy evidence– Both advisory panels concluded that many

allergenic extracts lack sufficient evidence of efficacy

– In our current review, FDA failed to identify supportive efficacy data for hundreds of products

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Panel recommendationsClassification panel 1974-1979 (601.25)

DiagnosisTherapy

(foods not included)

I 26% 1%

II 0% 0%

IIIA 48% 65%

IIIB 26% 34%

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Panel recommendations Reclassification panel 1982-1983 (601.26)

DiagnosisTherapy

(foods not included)

I 83% 67%

II 17% 33%

excludes IIIB foods/insects

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Panel recommendations Reclassification panel 1982-1983 (601.26)

DiagnosisTherapy

(foods not included)

I 73% 59%

II 27% 41%

includes IIIB foods/insects

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Paths forward

• Reasons to take action on the basis of efficacy evidence– Both advisory panels concluded that many

allergenic extracts lack sufficient evidence of efficacy

– In our current review, FDA failed to identify supportive efficacy data for hundreds of products

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Paths forward

• Other approaches

– Action under other regulations• 21 CFR 601.5• This regulation is applicable to all licensed

products; unlike 601.25 and 601.26, its application is not limited to products licensed before 1 July 1972.

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21 CFR 601.5§ 601.5 Revocation of license.…(b)(1) The Commissioner shall notifythe licensed manufacturer of the intentionto revoke the biologics license,setting forth the grounds for, and offeringan opportunity for a hearing on theproposed revocation if the Commissionerfinds any of the following:…(vi) The licensed product is not safeand effective for all of its intended usesor is misbranded with respect to anysuch use.

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• FDA would focus on products where there are safety concerns and where product efficacy is not supported by data

• FDA could bring actions to revoke licenses under §601.5, for allergenic extracts in Tables 4 and 5

21 CFR 601.5

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Other potential actions for products in Tables 1-3

• Nomenclature corrections: work with manufacturers to– Rename ambiguous products– Eliminate redundancies based on nomenclature– Eliminate mixes

• Indication corrections– Some extracts in Table 3 need to be relabeled “for

diagnostic use only”

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Paths forward

• 21 CFR 601.25 and 601.26• Other approaches:

– use 21 CFR 601.5 to address evidence of efficacy along with safety issues (Tables 4 and 5)

– work with manufacturers to address and correct nomenclature issues and indications (Tables 1-3)

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Today’s presentations

• Background• Allergenics efficacy reviews

– Panel 1, 21 CFR 601.25 (1974-1979)– Panel 2, 21 CFR 601.26 (1982-1983)

• Current evaluation process (2003-2011)• Safety of allergenic extracts• Assessments• Next steps

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Discussion points

• Comments on– the review process so far; – the decision to list non-standardized

allergenic products in five tables according to the evidence collected; and

– the possible disposition of the categories of products identified in the Tables